One Health Advancement of RABI-767 for the Management of Acute Pancreatitis

Project summary/abstract This proposal seeks the development of a novel therapeutic for acute pancreatitis, which is a major unmet medical need with no effective treatment in both human and veterinary medicine. Our approach builds upon a body of clinical and preclinical data that strongly implicate lipolysis and lipotoxicity as major driving factors in converting mild acute pancreatitis to severe, which is defined by sustained organ failure. In addition, this work is supported by data demonstrating that inhibition of lipase activity is able to abrogate the organ failure and indicators of systemic inflammatory response syndrome (SIRS) found in clinically relevant animal models of severe acute pancreatitis. Our status as a company is that we have a lead compound that has been validated in IND-enabling safety studies in dogs and rats, and multiple preclinical efficacy models with outstanding efficacy, as expounded below. We further have in place an expert team in the fields of clinical and translational research, pancreatitis research and treatment, entrepreneurship, business development, pharmaceutical partnering, and clinical trials. We are here proposing a companion animal trial to study the clinical response to RABI-767 using different dosing schedules, with two primary goals, 1) to establish the efficacy of RABI-767 in the treatment of spontaneous canine acute pancreatitis (CAP), and 2) to inform and optimize the treatment regimen for a phase 2 human clinical trial. This is expected to have a major impact on acute pancreatitis outcomes within a One Health framework, as recently advanced by the NIH and others. One Health encourages a holistic approach to human, animal, and environmental health. In light of our strong feasibility data, we are submitting this as a Phase IIb proposal, which will allow us to complete the key missing step in our commercial development plan, which is to optimize the dosing schedule for clinical use in both humans and canines. The objectives of this proposal are the completion of the following specific aims: Aim 1: Initiate a canine companion clinical trial to evaluate RABI-767 as a novel therapeutic for canine acute pancreatitis. Year 1 milestones: 1) drug product manufacturing suitable to initiate the companion animal trial, 2) initiation of enrollment in the companion animal trial. Aim 2: Establish the therapeutic efficacy of RABI-767 delivered to canines presenting with CAP using multiple dosing schedules. The Milestones of this aim include the significant improvement of clinical signs of CAP, and significant reduction of CRP within 3 days following administration of RABI-767 relative to the placebo control. At the completion of this proposal, we will have an IND-ready asset, with a committed, experienced, and successful clinical development team ready to take it through clinical trials.